title: Extractables characterization for five materials of construction representative of packaging systems used for parenteral and ophthalmic drug products.
abstract: Polymeric and elastomeric materials are commonly encountered in medical devices and packaging systems used to manufacture, store, deliver, and/or administer drug products. Characterizing extractables from such materials is a necessary step in establishing their suitability for use in these applications. In this study, five individual materials representative of polymers and elastomers commonly used in packaging systems and devices were extracted under conditions and with solvents that are relevant to parenteral and ophthalmic drug products (PODPs). Extraction methods included elevated temperature sealed vessel extraction, sonication, refluxing, and Soxhlet extraction. Extraction solvents included a low-pH (pH = 2.5) salt mixture, a high-pH (pH = 9.5) phosphate buffer, a 1/1 isopropanol/water mixture, isopropanol, and hexane. The resulting extracts were chemically characterized via spectroscopic and chromatographic means to establish the metal/trace element and organic extractables profiles. Additionally, the test articles themselves were tested for volatile organic substances. The results of this testing established the extractables profiles of the test articles, which are reported herein. Trends in the extractables, and their estimated concentrations, as a function of the extraction and testing methodologies are considered in the context of the use of the test article in medical applications and with respect to establishing best demonstrated practices for extractables profiling of materials used in PODP-related packaging systems and devices.
  Plastic and rubber materials are commonly encountered in medical devices and packaging/delivery systems for drug products. Characterizing the extractables from these materials is an important part of determining that they are suitable for use. In this study, five materials representative of plastics and rubbers used in packaging and medical devices were extracted by several means, and the extracts were analytically characterized to establish each material's profile of extracted organic compounds and trace element/metals. This information was utilized to make generalizations about the appropriateness of the test methods and the appropriate use of the test materials.
authors.affiliation: Baxter Healthcare Corporation, Round Lake, IL, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Jenke
authors.forename: James
authors.initials: J
authors.lastname: Castner
authors.forename: Thomas
authors.initials: T
authors.lastname: Egert
authors.forename: Tom
authors.initials: T
authors.lastname: Feinberg
authors.forename: Alan
authors.initials: A
authors.lastname: Hendricker
authors.forename: Christopher
authors.initials: C
authors.lastname: Houston
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Hunt
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
authors.forename: Arthur
authors.initials: A
authors.lastname: Shaw
authors.forename: Kumudini
authors.initials: K
authors.lastname: Nicholas
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Norwood
authors.forename: Diane
authors.initials: D
authors.lastname: Paskiet
authors.forename: Michael
authors.initials: M
authors.lastname: Ruberto
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Smith
authors.forename: Frank
authors.initials: F
authors.lastname: Holcomb
mesh_terms: D004340:Drug Contamination; D016503:Drug Delivery Systems; D004349:Drug Packaging; D008422:Materials Testing; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010969:Plastics / Q000737:chemistry; D019064:Product Packaging; D012408:Rubber
chemical_list: D004364:Pharmaceutical Preparations; D010969:Plastics; D012408:Rubber
keywords: Cyclic olefin copolymer; Extractables; Leachables; Low-density polyethylene; Plasticized poly (vinyl chloride); Polycarbonate; Polymer analysis; Rubber